The long term goal of this research is to develop methods and instrumentation to obtain improved quantification of the radioisotope distribution in humans and animals. SPRINT II is a third generation SPECT instrument developed as part of this ongoing effort. The focus of this proposal is to investigate two innovative approaches to SPECT imaging based on our previous work which have the potential for measurably increasing data accuracy and improving signal-to-noise ratios: 1. Determine the value of acquiring a vertex view of the brain during a conventional SPECT acquisition and incorporating this information into the image reconstruction or parameter estimation process. 2. Investigate the Compton scatter aperture for SPECT imaging with a variety of new second detector geometries and analyze systems which include multiple scattering and polarization effects in the scatter aperture. Models to be considered will include the possibility of combining a pinhole aperture for imaging unscattered photons. Object dependence and dependence on sampling will be considered, and performance will be compared to conventionally collimated systems designed for the same field of view and the same geometric resolution at the center of the field of view. Evaluation of these imaging methods will be accomplished using analysis of lower bounds, simulation, and small scale experiments. Biased bounds will be used to measure the performance of image reconstruction algorithms for data acquired from these systems.